Chiral Bis(guanidino)iminophosphoranes
1127
entry 1).[4] In contrast, the symmetry is significantly perturbed
in the crystalline state of (P)-1aꢀHBr (Fig. 2b).[12] The two
phenyl rings of one of the two DPENs occupy the pseudo-
equatorial positions, while those of the other occupy pseudo-
axial positions. Furthermore, the directions of the N–H bonds
are opposite to each other, hence a single hydrogen bond is
formed between the bromide anion and the N–H proton of
the individual bis(guanidino)iminophosphorane. It seems that
the disrupted symmetry of (P)-1aꢀHBr is responsible for the
low enantioselectivity (Table 2, entry 2). However, as shown
in Fig. 2c, (P)-1cꢀHBr exhibits entirely different structural
features in spite of having the same helical chirality as
(P)-1aꢀHBr. It possesses nearly C2-symmetry in the crystalline
state, although the direction of the two N–H bonds is opposite to
each other as observed in (P)-1aꢀHBr. The change in the
absolute configuration of products 9 between the reactions using
(P)-1aꢀHBr and (P)-1cꢀHBr may be caused by the structural
differences in these salts (Table 2, entry 2 vs 8). It should be
pointed out that the C2-symmetry of the catalyst framework as
observed in (M)-1aꢀHBr (Fig. 2a) and (P)-1cꢀHBr (Fig. 2c) is
key to establishing enantioselective transformations and is a
feature of the generally accepted strategy in developing efficient
enantioselective catalysts.
(a)
(b)
(c)
In conclusion, we synthesized uncharged chiral bis(guani-
dino)iminophosphorane organosuperbase catalysts substituted
by bulky aryl groups to confirm the effect of the aryl groups.
We first modified the synthetic procedure for the 7,7-membered
spiro-cyclization step to enhance the chemical yield of bis
(guanidino)iminophosphoranes. Although the isolated yield
of bis(guanidino)iminophosphorane could not be improved
markedly, bis(guanidino)iminophosphoranes having bulky aryl
substituents were newly synthesized according to the amended
procedure. These novel bis(guanidino)iminophosphoranes were
evaluated as chiral organosuperbase catalysts in the enantio-
selective amination of 2-methyltetralone. The introduction of
sterically bulky substituents such as 2,4,6-trimethylphenyl
groups led to further development of an efficient chiral organo-
superbase catalyst. Furthermore, the (P)-isomer with 1-naphthyl
substituents afforded the opposite enantiomer to that obtained
using other catalysts. Thus, these catalysts were found to be
potentially useful as enantioselective organosuperbase cata-
lysts. Further application of the newly synthesized bis(guani-
dino)iminophosphoranes in developing efficient enantioselective
transformations and elucidating the origin of stereochemical
outcomes are being investigated.
Fig. 2. X-ray single-crystal analysis of (a) (M)-1aꢀHBr; (b) (P)-1aꢀHBr;
and (c) (P)-1cꢀHBr. The protonated bis(guanidino)iminophosphoranes
and bromide anion are represented by tubes and spheres respectively. The
solvent molecules are omitted for clarity.
absolute stereochemistry of product 9 depends on the helical
chirality around the phosphorus centre of 1c. The enantioselec-
tivity obtained by using (P)-1c is not significant in the present
reaction. However, taking into consideration the fact that the
(P)-isomer did not function as an efficient enantioselective
catalyst in our previous report,[4] as observed in the reaction
using (P)-1a (Table 1, entry 2) and 1b, it can be presumed that
(P)-1c with 1-naphthyl substituents is potentially applicable to
other enantioselective transformations as a chiral organosuper-
base catalyst.
Finally, in order to gain an insight into the differences in
the stereochemical outcomes of the reactions using (M)-1a,
(P)-1a, and (P)-1c, we conducted single-crystal X-ray diffrac-
tion analysis of these HBr salts (Fig. 2).[11] As shown in Fig. 2a
and 2b, the structural features of (M)-1aꢀHBr and (P)-1aꢀHBr are
quite similar to those of analogous bis(guanidino)imino-
phosphorane substituted by benzyl groups, instead of methyl
ones, at the guanidine nitrogen atom, as reported in our previous
study.[4] Indeed, (M)-1aꢀHBr possesses a nearly C2-symmetric
structure[12] and the two N–H moieties attached at the central
phosphorus atom interact with the bromide anion through two
hydrogen bonds. It is likely that these two N–H moieties coupled
with the C2-symmetry of (M)-1aꢀHBr are favourable for achiev-
ing high enantioselectivity in the amination reaction (Table 2,
Supplementary Material
Representative experimental procedures and spectral data for
bis(guanidino)iminophosphorane catalysts and the amination
products are available on the Journal’s website.
Acknowledgement
This work was partially supported by a Grant-in-Aid for Scientific Research
on Innovative Areas ‘Advanced Molecular Transformations by Organoca-
talysts’ from MEXT, Japan, and a Grant-in-Aid for Scientific Research from
the JSPS. We gratefully acknowledge Mr Shohei Kawasaki (Daiichi Sankyo
Co., Ltd) for his kind support for the X-ray crystallographic analysis.
References
[1] (a) For reviews on organobase catalysis, see: C. Palomo, M. Oiarbide,